Phoebe Ahn
A delicate rustle sounds, no louder than a leaf falling to the autumn ground. First a small crack appears. Then more and more spider web across the thin papery wall of the chrysalis. Shuddering and squirming, a small something, wet and crumpled emerges from its deep slumber. Wings slowly unfurl revealing an unassuming tan pattern, the exact color of leaves on an autumnal afternoon. Six spindly legs gripping the stem of a fresh leaf, it tests its newest appendages. Open, close. Open, close. A swath of chestnut brown striped with brilliant orange and spotted with iridescent periwinkle exposed in the wing’s dorsal view. A flap to a flutter, and a flutter to flight, the buckeye butterfly completes its life cycle. As beautiful and delicate butterflies appear, staring at their intricate wing patterns, one might begin to wonder, where do these adornments come from? Why are there so many patterns? How are these designs determined? The answer lies in genetics.
Jeanne McDonald, a PhD candidate in the Department of Ecology and Evolutionary Biology at Cornell University, is currently working at the Reed lab. She is researching the developmental genes behind the intricacies of such butterfly patterns in addition to how they have evolved and diverged over centuries to create the multitude of color patterns we see in nature today.
Historically, the field of genetics has been a fickle subject to study as it can really only be analyzed indirectly and operates on a largely microscopic level. However, McDonald explains that “[w]e now have excellent tools for understanding the genetics of butterflies […] We use CRISPR/Cas9 to delete small bits of DNA to understand what role a gene plays in development. There are also now many labs studying butterfly genetics, so there are many more genome assemblies and resources than there used to be.” Genomes can be thought of as large instruction manuals, detailing how an organism appears, functions, and develops. In essence, the sentences represent DNA. CRISPR/Cas9 technology is essentially a word editing feature for genes. This gene editing technique allows a geneticist to cut a specific part of the DNA sentence and replace it with a different set of DNA. The Cas9 enzyme acts as “‘molecular scissors’ to snip DNA at a location specified by a guide RNA,” with the guide RNA being a valet for the Cas9 enzyme by helping it locate the sequence to cut. McDonald’s research centers upon identifying genes that appear to have some significance in wing pattern development. Then, using CRISPR/Cas9 gene editing techniques to snip away these specific genes in butterfly eggs and inserting a different gene. By rearing these caterpillars to adulthood, and observing whether their wing patterns have changed or not, and if so what changes occurred, McDonald can slowly, but surely identify the functions of each gene in the entire butterfly genome.
As such, a typical day of work for McDonald can vary from working physically in the lab, pipetting minuscule amounts of enzymatic liquid into slightly less diminutive volumes of liquid, to working on the computer analyzing gene sequences. In stark contrast, she is also tasked with, quite literally, venturing out of the lab into a field, geared with a butterfly net.
Aside from the microscopic scale, from a broader point of view McDonald’s work also contributes to a larger concept: evolution. As mentioned before, butterfly wing patterns are multitudinous, varied, and complex. Different species have diverged and converged for several millions of years. McDonald explained in an interview, “comparing the genetics of these patterns across species has led to some remarkable discoveries, such as that the same genes lay the groundwork for color pattern across species with very different patterns.” Mapping the butterfly genome and identifying their function can give us clues about the giant family tree of butterflies, and the even broader history about insects.
Though McDonald's interest in science began as early as middle school when her mother’s cousin introduced her to the Abbot Laboratory where she worked at the time, the beginning of her journey in genetics began while she was a biology major at Lake Forest College. As a student, she participated in research at the Shingleton lab on gene-environmental interactions. She states, “I became really fascinated with the genetics and developmental processes that give rise to the natural variation that first captivated me all those years ago."
As an undergraduate student, McDonald opens up in an interview about how her combined creativity for experimental ideas and her love for data analysis ultimately initiated the start of her PhD work at Cornell University. She explains that the articles from Cornell’s Reed Laboratory about “integrated genetics, developmental biology, and evolution” piqued her interest. Soon afterward, she reached out to Professor Robert Reed, applied to the program, and continues to work there to this day. However, despite the Ivy League label and impressive work within biochemistry she presently partakes in, she also admits that she did encounter some feelings of insecurity along the way. There were times when she questioned whether the PhD path was something she could really pursue or if she would even be admitted into a graduate program. She credits her college professors for encouraging her to reach beyond the ceiling her doubts had placed on her mind.
So far, McDonald has worked with the Buckeye butterfly (Junonia coenia), the Painted Lady butterfly (Vanessa cardui), and the Longwing butterfly (Heliconius), and she hopes to work with more in the future as she further dives into her research. McDonald assures us that despite all of the trial-and-error, confronting molecular techniques falling through, and long multi step procedures that could develop issues along any step of the way, the process is “ultimately rewarding when it finally works, […] I have changed the focus of my thesis in both my undergraduate and graduate work. I think the process of exploring those projects contributed a lot to my growth as a researcher.” As Remy from the Pixar movie Ratatouille states so succinctly, “the most predictable thing about life is its unpredictability,” McDonald also retrospectively commented that her educational journey has taught her about life’s twists and turns as she missed some schooling in her younger years due to a severe illness, then a pandemic attenuated some of her academic experience in her graduate school years. She gratefully admits, “I don’t know where I would be without all of the support from my mentors, teachers, family, and friends.” When asked about her future a decade later, McDonald replies that she hopes to still be conducting research and perhaps also teaching as a professor, in a way, giving back to the professors from her youth.
As McDonald continues her work, the future of butterfly genetics mirrors her own career as an exciting and unpredictable domain. Even if insects are not necessarily a great interest of everyone’s, this research is actually applicable to the general public in many ways. During the 20th century, gene conservation was investigated. This revealed that, despite differing patterns of expression, certain segments of DNA are more ancient than we originally expected. Some of these genes are present across multiple species from the buckeye butterfly to a human child, affecting the development of different tissues. However, as we shed more light on areas we were previously unaware of, new questions arise about these conserved genes: How much do these gene interactions vary from species to species? Do evolutionary forces prevent these genes from changing or are they simply retired every once in a while? How are the new traits linked to the older gene networks? McDonald hopes to compare networks across traits and species to perhaps help answer some of these challenging questions. Moreover, the techniques used to analyze these butterflies are not constrained to just insects. There is speculation that CRISPR/Cas9 technology is a mere leap away from entering the healthcare industry. According to a 2019 research paper about lung cancer, gene-editing may be used to evaluate genes and “identify new pathways to reduce or eliminate resistance to chemotherapy” in lung cancer patients. The word genetics may not be the first thing that comes to mind when one thinks of butterflies, but this creature, delicate and unassuming as it may be, provides a wealth of genetic information about our past, present, and future.
References
CRISPR Therapeutics. (2022) ‘CRISPR/Cas9’, CRISPR Therapeutics, available: http://www.crisprtx.com/gene-editing/crispr-cas9 [accessed 9 July 2022].
Jiang, C., Lin, X., Zhang, Z. (2019) ‘Applications of CRISPR/Cas9 Technology in the Treatment of Lung Cancer’, CellPress. August 15, available: https://www.cell.com/trends/molecular-medicine/fulltext/S1471-4914(19)30184-4 [accessed 9 July 2022].
MedlinePlus Genetics. (2022) ‘What are genome editing and CRISPR-Cas9’, National Library of Medicine. August 3, available: https://medlineplus.gov/genetics/understanding/genomicresearch/genomeediting/ [accessed 9 July 2022].